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Biomedical subjects

D S Thompson

Publications and source records attributed to D S Thompson.

At least 19 recordsLinked to original sources
PubMed1995

A phase I study of etoposide phosphate administered as a daily 30-minute infusion for 5 days.

PURPOSE: To determine the maximum tolerated dose, toxicities, kinetics, and disposition of etoposide phosphate when administered as a daily 30-minute infusion for 5 days. PATIENTS AND METHODS: Twenty-eight patients were enrolled in this phase I dose-escalation trial. Cohorts of patients received etoposide phosphate in etoposide equivalent doses of 50, 75, 100 and 125 mg/m2 intravenously for 30 minutes each day for 5 days. Pharmacokinetic sampling of both blood and urine was performed and concentrations of etoposide and etoposide phosphate were determined on day 1 of study for each patient and on day 4 of study for three patients receiving the 100 mg/m2 dose. RESULTS: The dose-limiting toxicity was reversible myelosuppression as evidenced by leukopenia and neutropenia. Toxicities seen were comparable to those expected from etoposide administration. With this schedule, the 100 mg/m2 dose was the maximum tolerated dose. Nonhematologic toxicities were generally mild. Two patients had major responses and three others had minor responses. Pharmacokinetic analyses revealed rapid (< 15 minutes) extensive conversion of etoposide phosphate to etoposide. Peak plasma etoposide concentrations and etoposide areas under the curve were proportional to the dose of etoposide phosphate administered. Etoposide kinetics were similar to those expected after a comparable dose of etoposide. CONCLUSIONS: Etoposide phosphate is a water-soluble pro-drug of etoposide that is rapidly converted to etoposide in vivo with a toxicity profile similar to etoposide. Etoposide generated from etoposide phosphate exhibits linear kinetics over a dose range of 50 to 125 mg/m2. When administered as a daily 30-minute infusion for 5 days, the dose-limiting toxicity is myelosuppression and 100 mg/m2 daily is the maximum tolerated dose.

Adult↗
PubMed1995

Paclitaxel by 1-hour infusion: an active drug in metastatic non-small-cell lung cancer.

PURPOSE: Paclitaxel is an active single agent when administered as a 24-hour continuous infusion in the treatment of stage IV non-small-cell lung cancer. We evaluated the efficacy and toxicity of paclitaxel administered by 1-hour infusion in the outpatient setting to patients with stage IV or relapsed non-small-cell lung cancer. PATIENTS AND METHODS: Fifty-nine patients with stage IV or relapsed non-small-cell lung cancer were treated with 1-hour infusions of paclitaxel. The first 17 patients received a dose of 135 mg/m2 and the remaining 42 patients received 200 mg/m2. By random assignment, 31 patients received a single-day, 1-hour infusion of paclitaxel, and 28 patients received a 3-day, divided-dose schedule, with each dose administered by 1-hour infusion. Both regimens were repeated every 21 days. All patients received premedication with dexamethasone, diphenhydramine, and cimetidine. Cytokines were not routinely used. RESULTS: Thirteen of 53 assessable patients (25%) had partial responses to treatment. An additional five patients had minor responses. The median survival duration of the entire group was 8 months and the actuarial 1-year survival rate was 33%. Patients who received 200 mg/m2 of paclitaxel had a higher response rate than those who received 135 mg/m2 (31% v 12%, respectively). Six of 16 patients (38%) previously treated with cisplatin-based regimens responded to 200 mg/m2 of paclitaxel. No significant differences in activity were seen when the 1-day and 3-day paclitaxel schedules were compared. Paclitaxel was well tolerated at both doses and schedules, and no severe hypersensitivity reactions occurred. Only 18 of 154 courses (12%) given at 200 mg/m2 resulted in grade 3 or 4 leukopenia. CONCLUSION: Paclitaxel administered by 1-hour infusion is an active and well-tolerated new agent in the treatment of metastatic non-small-cell lung cancer. These results suggest that a paclitaxel dose of 200 mg/m2 is more effective than 135 mg/m2 and can produce responses in patients previously treated with cisplatin-based regimens. Incorporation into combination regimens is indicated.

Adult↗
PubMed1990

Oxygen desaturation in women in labor.

Oxygen saturation and end-tidal CO2 tension were monitored in 15 healthy women during labor. Oxygen saturation was determined with a pulse oximeter and end-tidal CO2 with a CO2 monitor. Fetal heart rate, uterine contractions and maternal blood pressure were also monitored. End-tidal CO2 tension was followed to determine if falls in oxygen saturation during labor were related to hyperventilation. Ten of the 15 patients exhibited periods of oxygen saturation of less than 90%. End-tidal CO2 was consistently low, usually less than 30 mm Hg. Most, but not all (7 of 10), of the patients who showed desaturation had received narcotics. There were often periods of apnea and/or shallow respirations between contractions. These aberrations and hyperventilation-induced hypocarbia were probably the cause of the oxygen desaturation. No changes in fetal heart rate or low Apgar scores were noted.

Adolescent↗
PubMed1988

Granulocytic sarcoma of the small intestine preceding acute myelomonocytic leukemia with abnormal eosinophils and inv(16).

We report a case of preleukemic granulocytic sarcoma of the small intestine preceding the development of acute myelomonocytic leukemia with abnormal eosinophils and inversion of chromosome 16, inv(16)(p13q22). A literature review suggests that this is a recurring cytogenetic-clinicopathologic association and carries a favorable prognosis, especially if treated aggressively with antileukemic therapy at the time of diagnosis.

Chromosome Inversion↗
PubMed1988

The Hollywood surgical-audit programme: a computer-based discharge and data-collection system for surgical audit.

This article describes the development of a computer-based system for the prospective collection of data for surgical audit and peer review with the generation of a surgical discharge letter. The software has been developed for an IBM personal computer and is suitable for any compatible computer. The system has potential advantages for teaching hospitals as it enables patients to obtain a definitive discharge letter on their discharge from hospital. It is also of potential benefit to surgeons who wish to collect clinical data and to audit the quality of their surgical practice.

Computers↗
PubMed1986

Effects of verapamil on haemodynamic function and myocardial metabolism in patients with hypertrophic cardiomyopathy.

The effect of 20 mg dose of intravenous verapamil was studied over a range of heart rates in 12 patients with hypertrophic cardiomyopathy. Six patients had an appreciable left ventricular outflow tract gradient and six did not. The drug reduced myocardial oxygen consumption in proportion to a reduction in the development of left ventricular pressure. The negative inotropic effect of verapamil was counteracted by the drug's non-specific vasodilator activity, so that cardiac index was unaltered at any heart rate and as a result myocardial efficiency was unaffected by the drug. Verapamil did not consistently alter myocardial metabolism. Some patients showed improvement in anaerobic myocardial metabolism after verapamil but an equal number showed impairment of lactate metabolism. It was not possible to predict from clinical features, echocardiographic findings, or haemodynamic variables measured before administration of verapamil which patients would demonstrate haemodynamic or metabolic improvement after the drug. In this short term study no mechanism was demonstrated by which patients with hypertrophic cardiomyopathy might obtain a consistent improvement from treatment with verapamil.

Adolescent↗
PubMed1986

Higher than expected prevalence of multiple sclerosis in northern Colorado: dependence on methodologic issues.

A population-based study of multiple sclerosis (MS) was conducted in 2 northern Colorado counties in 1982 to determine MS prevalence, to compare the rates with recent North American surveys and to compare the methods used in these studies. Provisional cases were identified from: the patient rolls of MS service organizations, chart reviews in 2 neurology practices, a survey of physicians and a review of hospital discharge diagnoses. Crude-point prevalence for the 2-county region was 84 per 100,000. The age-adjusted rate was higher than the rate for the region above the 37th parallel projected from data in a 1976 national survey, but was comparable to rates obtained in localized surveys conducted in the northern tier of the country. The methodological results revealed that the highest yield sources were the MS service organizations and the neurology practice chart reviews. MS prevalence surveys which neglect these methods may underestimate MS prevalence by as much as 20-40%.

Adult↗
PubMed1986

The effects of pregnancy in multiple sclerosis: a retrospective study.

We reviewed the medical records of 178 women with multiple sclerosis to evaluate the number of completed pregnancies, current disability status, and relationship of pregnancy to onset of MS symptoms. We found no differences in the long-term disability of women with no pregnancies, one pregnancy, or two or more pregnancies. Women who had initial symptom onset in pregnancy experienced less subsequent disability than women whose symptoms began before or after pregnancy. Therefore, pregnancy per se or number of pregnancies has no effect on subsequent disability.

Adult↗
PubMed1985

Post-tubal sterilization syndrome--a misnomer.

Menstrual parameters and gynecologic symptoms of 389 women who underwent laparoscopic tubal banding were studied prospectively and longitudinally. Previous oral contraceptive users exhibited an immediate increase in menstrual flow and dysmenorrhea, which declined slightly with time. No such changes occurred in women who used other methods of temporary contraception. A significant increase in noncyclic pelvic pain, independent of previous contraceptive usage, developed only in women greater than 38 years of age. Menstrual cycles and dyspareunia were not affected. A small control group of women whose husbands underwent vasectomy showed no significant changes in any of these parameters.

Adult↗
PubMed1985

Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. II. Studies with monoclonal antibodies and terminal transferase.

A panel of 19 monoclonal antibodies (McAb) and the enzyme terminal transferase (TdT) have been applied to the characterization of poorly differentiated blasts from 50 patients with chronic granulocytic leukaemia (CGL) and myelofibrosis in blast crisis (BC), acute myelofibrosis and undifferentiated leukaemia. These cells were also extensively studied by transmission electron microscopy (TEM) (see Polli et al, 1985a). McAb against platelet glycoproteins (GP) showed a high specificity for megakaryoblasts, in particular those reactive with the GPIIb/IIIa complex (J15) and GPIIIa (C15 and C17), which were positive in a higher proportion of blasts than the McAb to GPIb (AN51 and FMC25). Findings with these anti-platelet McAb paralleled those of the platelet-peroxidase (PPO) reaction in 76% of cases studied simultaneously. The PPO reaction was always positive in cases in which two or more of the McAb were reactive with the blast cells. The differences observed suggest, nevertheless, that PPO is more sensitive for megakaryoblasts than the McAb and that this TEM technique should be reserved for cases which are negative with the platelet specific McAb. Of the McAb against myeloid antigens used in this series OKM1 was positive in 50% of cases but the others failed to demonstrate early features of differentiation in myeloblasts and monoblasts. In only three cases were erythroid precursors demonstrated by TEM and these were the only ones reactive with a McAb to glycophorin-A (LICR LON/R10). TdT and the McAb J5 helped in the identification of lymphoblasts which were seen as a 'pure' proliferation in 23% of CGL-BC and as part of blast cell mixtures in another 17% of cases. The McAb reactive to haemopoietic precursor cells (RFB1, FMC8 and OKIa), on the other hand, were of no practical value for the classification of blast cell types. The lineage specificity of several of the McAb used in this study, confirmed by TEM, suggest that these reagents are valuable tools for the characterization of immature blast cells.

Acute Disease↗
PubMed1985

Effects of intracoronary and intravenous amrinone infusions in patients with cardiac failure and patients with near normal cardiac function.

The effects of intracoronary and intravenous infusions of amrinone were studied to distinguish the drug's direct cardiac actions from its peripheral vascular and neuroendocrine properties. Intracoronary infusions of amrinone were found to have no haemodynamic effect other than producing a slight reduction in the left ventricular ejection fraction and some suggestion of coronary vasodilatation in patients with impaired left ventricular function. They did not improve contractility, cardiac output, or filling pressures and had no significant effect on myocardial metabolism, although therapeutic concentrations of the drug were detected in coronary sinus blood. Intravenously administered amrinone reduced filling pressures and improved the cardiac index in all patients, but haemodynamic improvements were most pronounced in the patients with the worst cardiac function. These changes were accompanied by improvements in the indices of contractility only in patients in whom alterations in concentrations of free fatty acid, glycerol, and glucose suggested peripheral catecholamine release. In the patients with the best basal cardiac function intravenously administered amrinone produced a reduction in myocardial work and evidence of myocardial ischaemia, as a result of excessive reduction of coronary perfusion pressure and increased heart rate, without any appreciable increase in cardiac index. It is concluded that, at the concentrations of the drug that can be achieved in man without adverse effects, amrinone has no direct positive inotropic effect. Haemodynamic changes are predominantly the result of vasodilatation, although catecholamines may be released in some patients.

Adult↗
PubMed1985

Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure.

Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose.

Adult↗
PubMed1984

Comparison of the effects of amrinone and sodium nitroprusside on haemodynamics, contractility, and myocardial metabolism in patients with cardiac failure due to coronary artery disease and dilated cardiomyopathy.

The effects of intravenous amrinone and sodium nitroprusside on haemodynamic indices, left ventricular contractility, and myocardial metabolism were compared in patients with cardiac failure. All patients received one dose of each drug and some received serial doses. Eight patients had dilated cardiomyopathy and six coronary artery disease, but the responses to the two drugs were independent of the aetiology of cardiac failure. Both drugs lowered left ventricular end diastolic pressure and aortocoronary sinus oxygen difference and increased cardiac index and left ventricular efficiency; these effects were dose related. Although the effects of the drugs on peripheral blood substrate concentrations were different, those on myocardial substrate metabolism were identical. Pressure derived indices of contractility in each group of patients were unaltered by either drug. After amrinone administration increases in cardiac index were related to plasma amrinone concentration, but alterations in contractility were not. In four individual patients increases in contractility were associated with alterations in plasma metabolite concentrations, which suggested that catecholamine release had occurred. For the groups of patients as a whole, however, amrinone had effects which did not differ significantly from those of the pure vasodilator, nitroprusside. There was no evidence that amrinone had a direct positive inotropic effect since no dose related changes in indices of contractile function could be established.

Adult↗
PubMed1983

Evoked potential abnormalities in myotonic dystrophy.

Past investigators have reported evidence of central nervous system involvement in myotonic dystrophy (MYD), including EEG abnormalities, ventricular enlargement, thalamic inclusion bodies, and impaired tests of cognitive function. Brain stem auditory evoked potentials have not been reported in myotonic dystrophy. We report the results of brain stem auditory (BAEP) and median nerve somatosensory (MSSEP) evoked potentials in 15 patients with MYD (9 males, 6 females, mean age = 35.8 +/- 11.4 years). BAEPs were abnormal in 53.3% (P less than 0.05). Four patients had abnormal wave I-III interwave latencies, 3 had abnormal wave III-V latencies, and 1 patient had both wave I-III and wave III-V latencies prolonged. MSSEPs were abnormal in 13.3% (P N.S.). Both patients showed a delay of the P15-N19 thalamic complex. Both patients had a normal clinical sensory examination and normal peripheral nerve conduction. No correlation was found between abnormal evoked potentials and patient age. A sex difference, however, was noted with 8/9 males having one or more abnormal evoked potentials compared with 0/6 females. Though our finding of abnormal MSSEPs was not statistically significant, both patients showed delay at the thalamic level, where pathology has been described. Abnormal ocular pursuit and sluggish pupillary reaction have implicated brain stem involvement in MYD. The abnormal BAEPs at the level of the pons and midbrain in this study provide neurophysiological evidence of brain stem pathology in MYD.

Adult↗
PubMed1983

Haemodynamic effects of intravenous amrinone in patients with impaired left ventricular function.

The effects of intravenous amrinone on resting haemodynamic function were investigated in 15 patients with impaired left ventricular function. All patients received 1 X 5 mg/kg and 10 received a further 2 mg/kg. We observed dose related increases in heart rate and cardiac index, and reductions in mean arterial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance. A small reduction in left ventricular end-diastolic volume and a 36% increase in ejection fraction occurred. No significant change in max dp/dt, min dp/dt, (Max dp/dt/P), max (dp/dt/P), KVmax or the ratio of left ventricular end-systolic pressure to left ventricular end-systolic volume was detected. It is concluded that the beneficial effects of intravenous amrinone on the resting haemodynamics in our patients were attributable to vasodilatation, with the drug having no demonstrable positive inotropic effect.

Adult↗